Genetic diversity and occult hepatitis B infection in Africa: A comprehensive review

BACKGROUND Occult hepatitis B infection(OBI)is a globally prevalent infection,with its frequency being influenced by the prevalence of hepatitis B virus(HBV)infection in a particular geographic region,including Africa.OBI can be transmitted th-rough blood transfusions and organ transplants and has been linked to the development of hepatocellular carcinoma(HCC).The associated HBV genotype influences the infection.AIM To highlight the genetic diversity and prevalence of OBI in Africa.METHODS This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and involved a comprehensive search on PubMed,Google Scholar,Science Direct,and African Journals Online for published studies on the prevalence and genetic diversity of OBI in Africa.RESULTS The synthesis included 83 articles,revealing that the prevalence of OBI varied between countries and population groups,with the highest prevalence being 90.9%in patients with hepatitis C virus infection and 38%in blood donors,indicating an increased risk of HBV transmission through blood transfusions.Cases of OBI reactivation have been reported following chemotherapy.Genotype D is the predominant,followed by genotypes A and E.CONCLUSION This review highlights the prevalence of OBI in Africa,which varies across countries and population groups.The study also demonstrates that genotype D is the most prevalent.

Perception of Medical Students towards Hepatitis B Virus Infection and Hepatitis B Vaccination in a Private Tertiary Hospital in Jos North Local Government, Plateau State, Nigeria

Background: Prevention is one of the safe schemes against the high prevalence of viral Hepatitis. Negative perceptions or perceptions about the risks of hepatitis B among medical students and health care workers may influence the behavioral pattern and adoption of preventive measures against the virus and can affect the uptake of the Hepatitis B vaccine. This study assesses the perception of medical students towards Hepatitis B virus infection and Hepatitis B Vaccination in a Private Tertiary Hospital in Jos North Local Government, Plateau State, Nigeria. Methods: This was a descriptive cross-sectional study done in August 2021 among 236 clinical medical students using a multistage sampling technique. Data was collected using an interviewer-administered structured questionnaire and analysed using the IBM SPSS 28 (Statistical Package for the Social Sciences). Ethical approval was granted by Bingham University Teaching Hospital, Ethics Committee, Jos, Plateau State. Results: Two-thirds of respondents were of the opinion that they are at risk of contracting HBV. Half were of the opinion that the risk is very much while a third believed the risk is moderate. Among those who think they are not at risk of contracting HBV, the majority felt so because they are vaccinated while 10.3% believe that they are safe. 43.2% of respondents think that HBV Vaccine is very effective in preventing HBV infection while 39.8% think it is slightly effective, and 7.6% think it is not effective. Almost all respondents, 99.2% are of the opinion that HBV Vaccination is important for students while 0.8% think it is not important. The majority of the respondents at 95.8% were willing to be screened for HBV. The majority (85.6%) of respondents are willing to pay for HBV Vaccine as against 14.4% of respondents who are not willing to pay. Conclusion: Summarily, 21 (8.9%) of the students had a negative perception of Hepatitis B Vaccination, and 215 (91.1%) had a positive perception of Hepatitis B Vaccination. Perception-sustaining events like seminars, workshops, road shows, and campaigns should be organized among students and health workers.

Hepatitis B virus infection in patients with Wilson disease:A large retrospective study

BACKGROUND Wilson disease(WD)is the most common genetic metabolic liver disease.Some studies have shown that comorbidities may have important effects on WD.Data on hepatitis B virus(HBV)infection in patients with WD are limited.AIM To investigate the prevalence and clinical impact of HBV infection in patients with WD.METHODS The clinical data of patients with WD were analyzed retrospectively,and the data of patients with concurrent WD and HBV infection were compared with those of patients with isolated WD.RESULTS Among a total of 915 WD patients recruited,the total prevalence of current and previous HBV infection was 2.1%[95%confidence interval(CI):1.2%-3.0%]and 9.2%(95%CI:7.3%-11.1%),respectively.The main finding of this study was the identification of 19 patients with concurrent WD and chronic hepatitis B(CHB)infection.The diagnosis of WD was missed in all but two patients with CHB infection.The mean delay in the diagnosis of WD in patients with concurrent WD and CHB infection was 32.5 mo,which was significantly longer than that in patients with isolated WD(10.5 mo).The rates of severe liver disease and mortality in patients with concurrent WD and CHB infection were significantly higher than those in patients with isolated WD(63.1%vs 19.3%,P=0.000 and 36.8%vs 4.1%,P<0.001,respectively).Binary logistic regression analysis revealed a significantly higher risk of severe liver disease at the diagnosis of WD in patients with current HBV infection[odds ratio(OR)=7.748;95%CI:2.890-20.774;P=0.000)]or previous HBV infection(OR=5.525;95%CI:3.159-8.739;P=0.000)than in patients with isolated WD.CONCLUSION The total prevalence of current HBV infection in patients with WD was 2.1%.The diagnosis of WD in CHB patients is usually missed.HBV infection is an independent risk factor for severe liver disease in WD patients.The diagnosis of WD should be ruled out in some patients with CHB infection.

Demyelinating neuropathy in patients with hepatitis B virus: A case report

BACKGROUND Hepatitis B rarely leads to demyelinating neuropathy,despite peripheral neuropathy being the first symptom of hepatitis B infection.CASE SUMMARY A 64-year-old man presented with sensorimotor symptoms in multiple peripheral nerves.Serological testing showed that these symptoms were due to hepatitis B.After undergoing treatment involving intravenous immunoglobulin and an antiviral agent,there was a notable improvement in his symptoms.CONCLUSION Although hepatitis B virus(HBV)infection is known to affect hepatocytes,it is crucial to recognize the range of additional manifestations linked to this infection.The connection between long-term HBV infection and demyelinating neuropathy has seldom been documented;hence,prompt diagnostic and treatment are essential.The patient's positive reaction to immunoglobulin seems to be associated with production of the antigen-antibody immune complex.

New therapeutic options for persistent low-level viremia in patients with chronic hepatitis B virus infection:Increase of entecavir dosage

Chronic hepatitis B virus(HBV)infection(CHB)is a public health concern worldwide.Current therapies utilizing nucleos(t)ide analogs(NA)have not resulted in a complete cure for CHB.Furthermore,patients on long-term NA treatment often develop low-level viremia(LLV).Persistent LLV,in addition to causing the progression of liver disease or hepatocellular carcinoma,may shed light on the current plight of NA therapy.Here,we review the literature on LLV,NA treatment,and various doses of entecavir to find a strategy for improving the efficacy of this antiviral agent.For LLV patients,three therapeutic options are available,switching to another antiviral monotherapy,interferon-αswitching therapy,and continuing monotherapy.In real-world clinical practice,entecavir overdose has been used in antiviral therapy for CHB patients with NA refractory and persistent LLV,which encouraged us to conduct further in-depth literature survey on dosage and duration related entecavir studies.The studies of pharmacodynamics and pharmacokinetics show that entecavir has the maximal selected index for safety,and has great potential in inhibiting HBV replication,in all of the NAs.In the particular section of the drug approval package published by the United States Food and Drug Administration,entecavir doses 2.5-20 mg/d do not increase adverse events,and entecavir doses higher than 1.0 mg/d might improve the antiviral efficacy.The literature survey led us to two suggestions:(1)Increasing entecavir dose to 1.0 mg/d for the treatment of NA naïve patients with HBV DNA>2×106 IU/mL is feasible and would provide better prognosis;and(2)Further research is needed to assess the long-term toxic effects of higher entecavir doses(2.5 and 5.0 mg/d),which may prove beneficial in treating patients with prior NA treatment,partial virological response,or LLV state.

Current therapeutic strategies for recurrent hepatitis B virus infection after liver transplantation

Hepatitis B virus (HBV)-related liver disease is the leading indication for liver transplantation (LT) in Asia,especially in China.With the introduction of hepatitis B immunoglobulin (HBIG) and oral antiviral drugs,the recurrent HBV infection rate after LT has been evidently reduced.However,complete eradication of recurrent HBV infection after LT is almost impossible.Recurrent graft infection may lead to rapid disease progression and is a frequent cause of death within the fi rst year after LT.At present,the availability of new oral medications,especially nucleoside or nucleotide analogues such as adefovir dipivoxil,entecavir and tenofovir disoproxil fumarate,further strengthens our ability to treat recurrent HBV infection after LT.Moreover,since combined treatment with HBIG and antiviral agents after liver re-transplantation may play an important role in improving the prognosis of recurrent HBV infection,irreversible graft dysfunction secondary to recurrent HBV infection in spite of oral medications should no longer be considered an absolute contraindication for liver re-transplantation.Published reviews focusing on the therapeutic strategies for recurrent HBV infection after LT are very limited.In this article,the current therapeutic strategies for recurrent HBV infection after LT and evolving new trends are reviewed to guide clinical doctors to choose an optimal treatment plan in different clinical settings.

Prevalence of occult hepatitis B virus infection in haemodialysis patients from central Greece

AIM:To assess the hepatitis B virus(HBV)-DNA and the prevalence of occult HBV infection in end-stage renal failure(ESRF)patients from Central Greece. METHODS:Sera from 366 ESRF patients attending five out of six dialysis units from Central Greece were investigated for HBV-DNA by real-time polymerase chain reaction.Only serum samples with repeatedly detectable HBV-DNA were considered positive.IgG antibodies to hepatitis C virus(anti-HCV)were tested by a third generation enzyme linked immunosorbent assay(ELISA),while IgG antibodies to hepatitis E virus (anti-HEV)were tested by two commercially available ELISAs.RESULTS:HBV-DNA was detected in 15/366 patient (4.1%)and HBsAg in 20/366(5.5%).The prevalenc of occult HBV infection was 0.9%(3/346 HBsAg negative patients).Occult HBV was not associate with a specific marker of HBV infection or anti-HCV o anti-HEV reactivity.There was no significant differenc in HBV-DNA titres,demographic and biochemica features,between patients with occult HBV infectio and those with HBsAg-positive chronic HBV infection. CONCLUSION:In central Greece,4%of ESRF patient had detectable HBV-DNA,though in this setting,th prevalence of occult HBV seems to be very low(0.9%).

Distribution of different hepatitis C virus genotypes in patients with hepatitis C virus infection

AIM:To investigate the presence of mixed infection and discrepancy between hepatitis C virus(HCV) genotypes in plasma,peripheral blood mononuclear cells(PBMCs),and liver biopsy specimens.METHODS:From September 2008 up to April 2009,133 patients with chronic hepatitis C referred to Firouzgar Hospital for initiation of an antiviral therapy were recruited in the study.Five milliliters of peripheral blood was collected from each patient and liver biopsy was performed in those who gave consent or had indications.HCV genotyping was done using INNO-LiPATM HCV in serum,PBMCs,and liver biopsy specimens and then conf irmed by sequencing of 5'-UTR fragments.RESULTS:The mean age of patients was 30.3 ± 17.1 years.Multiple transfusion was seen in 124(93.2%) of patients.Multiple HCV genotypes were found in 3(2.3%) of 133 plasma samples,9(6.8%) of 133 PBMC samples,and 8(18.2%) of 44 liver biopsy specimens.It is notable that the different genotypes found in PBMCs were not the same as those found in plasma and liver biopsy specimens.CONCLUSION:Our study shows that a signif icant proportion of patients with chronic hepatitis C are affected by multiple HCV genotypes which may not be detectable only in serum of patients.

Metabolic complications of hepatitis C virus infection

Hepatitis C virus(HCV) infection is a systemic disease that is implicated in multiple extrahepatic organ dysfunction contributing to its protean manifestations. HCV is associated with diverse extrahepatic disorders including atherosclerosis, glucose and lipid metabolic disturbances, alterations in the iron metabolic pathways, and lymphoproliferative diseases over and above the traditional liver manifestations of cirrhosis and hepatocellular carcinoma. The orchestration between HCV major proteins and the liver-muscle-adipose axis, poses a major burden on the global health of human body organs, if not adequately addressed. The close and inseparable associations between chronic HCV infection, metabolic disease, and cardiovascular disorders are specifically important considering the increasing prevalence of obesity and metabolic syndrome, and their economic burden to patients, the healthcare systems, and society. Cellular and molecular mechanisms governing the interplay of these organs and tissues in health and disease are therefore of significant interest. The coexistence of metabolic disorders and chronic hepatitis C infection also enhances the progression to liver fibrosis and hepatocellular carcinoma. The presence of metabolic disorders is believed to influence the chronicity and virulence of HCV leading to liver disease progression. This comprehensive review highlights current knowledge on the metabolic manifestations of hepatitis C and the potential pathways in which these metabolic changes can influence the natural history of the disease.

C–C motif chemokine ligand 16 inhibits the progression of liver cirrhosis via inactivating hepatic stellate cells

Background:Liver cirrhosis results from many forms of chronic damage,characterized by accumulation of extracellular matrix.The present study aimed to explore a potential non-invasive biomarker and its mechanism in the progression of liver cirrhosis.Methods:Gene Expression Omnibus(GEO)dataset(GSE15654,n=216)was analyzed to screen genes associated with progression of liver cirrhosis.A total of 181 plasma samples,including healthy control(HC,n=20),chronic hepatitis B(CHB,n=77)and HBV-related liver cirrhosis(LC,n=84),were enrolled for validation.In vitro and in vivo experiments were employed for the mechanistic investigation.Results:GEO dataset analysis showed that relatively low mRNA-expression of C–C motif chemokine ligand 16(CCL16)was associated with elevated Child-Pugh score(P=0.034)and worse prognosis(P=0.025).Plasma CCL16 level decreased in a stepwise pattern,with a median concentration of 10.29,6.57 and 4.47 ng/mL in the HC,CHB and LC groups,respectively(P<0.001).Low plasma CCL16 was significantly related to hepatic dysfunction both in the CHB and LC groups(P<0.05).Combination of CCL16 and ALT showed improved distinguishing capability for LC compared to either alone.In vitro,CCL16 expression was downregulated by lipopolysaccharide and hypoxia.Overexpression of CCL16 from human normal liver cell line(LO2)reduced the extracellular matrix associated proteins(Col1 and Col4)in human hepatic stellate cell line(LX-2).In vivo,the pathological feature of cirrhosis was alleviated by the hepatocytespecific expression of CCL16.Conclusions:CCL16 could be a feasible plasma marker to predict the occurrence and progression of liver cirrhosis.CCL16 might impact liver cirrhosis through inactivating hepatic stellate cells.

Occult hepatitis B virus infection and surgical outcomes in non-B, non-C patients with curative resection for hepatocellular carcinoma

AIM To investigate the prevalence, clinicopathological characteristics and surgical outcomes of occult hepatitis B virus(HBV) infection(OBI) in patients with non-B, non-C(NBNC) hepatocellular carcinoma(HCC).METHODS This study retrospectively examined the cases of 78 NBNC patients with curative resection for HCC for whom DNA could be extracted from formalin-fixed paraffin-embedded tissue. OBI was determined by the HBV-DNA amplification of at least two different sets of primers by TaqM an realtime polymerase chain reaction. Possibly carcinogenetic factors such as alcohol abuse, diabetes mellitus, obesity and non-alcoholic steatohepatitis(NASH) were examined. Surgical outcomes were evaluated according to diseasefree survival(DFS), overall survival(OS) and diseasespecific survival(DSS).RESULTS OBI was found in 27/78 patients(34.6%) with NBNC HCC. The OBI patients were significantly younger than the non-OBI cases at the time of surgery(average age 63.0 vs 68.1, P = 0.0334) and the OBI cases overlapped with other etiologies significantly more frequently compared to the non-OBI cases(P = 0.0057). OBI had no impact on the DFS, OS or DSS. Only tumorrelated factors affected these surgical outcomes.CONCLUSION Our findings indicate that OBI had no impact on surgical outcomes. The surgical outcomes of NBNC HCC depend on early tumor detection; this reconfirms the importance of a periodic medical examination for individuals who have NBNC HCC risk factors.

Previous hepatitis B viral infection–an underestimated cause of pancreatic cancer

BACKGROUND The etiology of pancreatic cancer remains unclear. This limits the possibility of prevention and effective treatment. Hepatitis B virus(HBV) is responsible for the development of different types of cancer, but its role in pancreatic cancer is still being discussed.AIM To assess the prevalence of previous HBV infection and to identify viral biomarkers in patients with pancreatic ductal adenocarcinoma(PDAC) to support the role of the virus in etiology of this cancer.METHODS The data of 130 hepatitis B surface antigen-negative subjects were available for the final analysis,including 60 patients with PDAC confirmed by cytology or histology and 70 sex-and age-matched controls. All the participants were tested for HBV biomarkers in blood [antibody to hepatitis B core antigen(anti-HBc), antibody to hepatitis B surface antigen(anti-HBs) and HBV DNA], and for those with PDAC, biomarkers in resected pancreatic tissues were tested(HBV DNA, HBV pregenomic RNA and covalently closed circular DNA). We performed immunohistochemistry staining of pancreatic tissues for hepatitis B virus X antigen and Ki-67 protein. Non-parametric statistics were used for the analysis.RESULTS Anti-HBc was detected in 18/60(30%) patients with PDAC and in 9/70(13%) participants in the control group(P = 0.029). Accordingly, the odds of PDAC in anti-HBc-positive subjects were higher compared to those with no previous HBV infection(odds ratio: 2.905, 95% confidence interval: 1.191-7.084, standard error 0.455). HBV DNA was detected in 8 cases of PDAC and in 6 of them in the pancreatic tumor tissue samples only(all patients were anti-HBc positive). Blood HBV DNA was negative in all subjects of the control group with positive results of the serum anti-HBc test. Among 9 patients with PDAC, 5 revealed signs of replicative competence of the virus(covalently closed circular DNA with or without pregenomic RNA) in the pancreatic tumor tissue samples. Hepatitis B virus X antigen expression and active cell proliferation was revealed by immunohistochemistry in 4 patients with PDAC in the pancreatic tumor tissue samples.CONCLUSION We found significantly higher risks of PDAC in anti-HBc-positive patients. Detection of viral replication and hepatitis B virus X protein expression in the tumor tissue prove involvement of HBV infection in pancreatic cancer development.

The association between the genetic polymorphisms of LMP2/LMP7 and the outcomes of HCV infection among drug users

Objective：To investigate a possible association of LMP2/LMP7 genes with chronic hepatitis C virus（HCV） infection,and to assess whether LMP2/LMP7 genes could influence the outcomes of HCV infection among drug users.Methods：Genomic DNAs of 362 anti-HCV sero-positive drug users and 225 control drug users were extracted from the peripheral blood leukocytes.The sero-positive patients were divided into those who had persistent infection and those who had spontaneously cleared the infection.Polymorphisms of LMP genes were determined by PCR combined with restriction fragment length polymorphism（RFLP）.Results：The distribution of LMP2 genotypes among the control,persistent infection and spontaneous clearance groups were not different.However,the LMP7 codon 145 Gln/Lys,Lys/Lys,and Gln/Lys＋Lys/Lys genotypes were found significantly more frequent in the persistent infection group than in control group（OR=1.75,95%CI=1.06～2.90;OR=3.16,95%CI=1.23-8.12;OR=1.94,95%CI=1.21-3.12,respectively）.Similarly,the frequencies of the codon 145 Gln/Lys,Lys/Lys,and Gln/Lys＋Lys/Lys genotypes were found significantly more frequent in the persistent infection group than in the spontaneous clearance group（OR=1.64,95%CI=1.04-2.57;OR=2.40,95%CI=1.09-5.28;OR=1.76,95%CI=1.152.69,respectively）.Stratified analysis indicated that combined genotype Gln/Lys＋Lys/Lys of the LMP7 gene was related to an increasing susceptibility to HCV infection（OR=1.91,95%CI=1.02-3.55;OR=2.19,95%CI=1.243.89;OR=1.91,95%CI=1.05-3.48,OR=2.86,95%CI=1.41-5.78,respectively）and the risk of persistent HCV infection（OR=1.94,95%CI=1.12-3.34;OR=2.02,95%CI=1.21-3.38;OR=1.78,95%CI=1.12-2.85,OR=2.23,95%CI=1.09-4.58,respectively）among30-year-old,males,the injection drug user（IDU）subjects and/or the shorter duration drug users（≤5 y）.Conclusion：These results suggest that polymorphism of the LMP7 gene may have an influence on the outcomes of HCV infection,and is one of the factors accounting for the genetic susceptibility to HCV infection among drug users.

High Prevalence of Hepatitis B Virus Infection Compared to Human Immunodeficiency Virus among Blood Donors in Bangui

Introduction: Hepatitis B Virus (HBV) and Human Immunodeficiency Virus (HIV) infection is a public health problem worldwide, particularly in sub-Saharan Africa. Objective: to compare the epidemiological, clinical and biological characteristics of chronic HBV and HIV infection in blood donors at the National Center for Blood Transfusion (NCBT) in Bangui. Patients and Methods: This was an 8-month analytical cross-sectional study from August 10, 2011 to April 9, 2012. During this study, we consecutively enrolled consenting blood donors of both sexes in which the search for HBsAg and HIV infection was carried out. Results: During the study period, 850 blood donors were collected. HBsAg was found in 142 donors (16.7%), of whom 55 blood donors (6.5%) were coinfected with HIV. On the other hand, HIV serology was positive in 77 blood donors (9.1%) including 55 co-infected (6.5%) with HBV. In order to better compare the risk factors, we have not included HIV-HBV coinfected patients. Only 795 blood donors were selected for the risk factor study. There were 87 cases of HBsAg positive (10.9%) and 22 cases of HIV positive (2.8%). The average age of HIV and HBV infected patients was 25.7 and 26.2 years, respectively. Twelve blood donors (1.5%) over the age of 20 were HBsAg versus 3 HIV positive blood donors (0.4%). Among blood donors over the age of 20, 75 (9.9%) were HBsAg positive, while 19 (2.4%) were HIV positive. Men were infected with HIV in 20 cases (2.5%), while those infected with HBV were 84 (10.6%). The risk factor found during HIV infection and HBV was unprotected sex with a p of 0.0038 and 0.0017 respectively. Conclusion: The prevalence of HBV infection is higher than that of HIV among blood donors in Bangui. The setting up of a national viral hepatitis control program, which will develop screening, treatment and vaccination actions could make the curve bend.

Hepatitis B virus infection reactivation in patients under immunosuppressive therapies:Pathogenesis,screening,prevention and treatment

With a 5.3%of the global population involved,hepatitis B virus(HBV)is a major public health challenge requiring an urgent response.After a possible acute phase,the natural history of HBV infection can progress in chronicity.Patients with overt or occult HBV infection can undergo HBV reactivation(HBVr)in course of immunosuppressive treatments that,apart from oncological and hematological diseases,are also used in rheumatologic,gastrointestinal,neurological and dermatological settings,as well as to treat severe acute respiratory syndrome coronavirus 2 infection.The risk of HBV reactivation is related to the immune status of the patient and the baseline HBV infection condition.The aim of the present paper is to investigate the risk of HBVr in those not oncological settings in order to suggest strategies for preventing and treating this occurrence.The main studies about HBVr for patients with occult hepatitis B infection and chronic HBV infection affected by non-oncologic diseases eligible for immunosuppressive treatment have been analyzed.The occurrence of this challenging event can be reduced screening the population eligible for immunosuppressant to assess the best strategies according to any virological status.Further prospective studies are needed to increase data on the risk of HBVr related to newer immunomodulant agents employed in non-oncological setting.

Emergency re-routing of anterior sector venous outflow for right lobe living donor liver transplantation including the middle hepatic vein

BACKGROUND:Controversy remains over whether the middle hepatic vein should be included in the liver graft in right liver living donor liver transplantation.Congestion in the anterior sector of a right liver graft can cause graft malfunction,which is especially devastating in the case of a graft with marginal size in relation to recipient body size on top of poor pre-transplant recipient status.The case we report here highlighted the importance of the middle hepatic vein in right liver living donor liver transplantation.METHODS:We illustrated the rectification of outflow obstruction of the middle hepatic vein in the anterior sector of right liver graft caused by technical error during transplantation.The rectification was performed with emergency re-routing using an artificial conduit.RESULT:Congestion in the anterior sector of the graft improved immediately and the patient’s postoperative liver function test results improved gradually.CONCLUSIONS:The middle hepatic vein is important for effective drainage of the anterior sector of a right liver graft.The re-routing technique described in the report can also be applied to cases in which the middle hepatic vein is injured during hepatectomy requiring immediate reconstruction.

Is chronic hepatitis C virus infection a risk factor for breast cancer?

AIM:To evaluate the prevalence of breast tumors in adult females with chronic hepatitis C virus(HCV) infection.METHODS:Prospective,single-center study,based on female outpatients consulting in a liver unit,for 1 year.The study group included females with present and/or past history of chronic infection by HCV.Patients with spontaneous recovery were excluded.Chronic hepatitis had been proved by liver biopsy in the majority of cases and/or biological markers of inflammation and fibrosis.The control group included female patients with other well documented chronic liver diseases:chronic hepatitis B,alcoholic liver disease,autoimmune hepatitis,hemochromatosis,non alcoholic liver disease,chronic cholangitis.Participating patients were prospectively questioned during consultation about past breast history and follow-up by mammography.RESULTS:Breast carcinoma was recorded in 17/294 patients with HCV infection(5.8%,95% CI:3.1-8.4) vs 5/107 control patients(4.7%,95% CI:0.67-8.67).Benign tumors of the breast(mastosis,nodules,cysts) were recorded in 75/294 patients with HCV infection(25.5%,95% CI:20.5-30.5) vs 21/107(19.6%,95% CI:12.1-27.1) in the control group.No lesion was noted in 202 patients with HCV(68.7%,95% CI:63.4-74) vs 81 control patients(75.7%,95% CI:67.6-83.8).Despite a trend to an increased prevalence in the group with HCV infection,the difference was not significant compared to the control group(P=NS).In patients over 40 years,the results were,respectively,as follows:breast cancer associated with HCV:17/266 patients(6.3%,95% CI:3.4-9.3) vs 5/95 patients(5.2%,95% CI:0.7-9.7) in the control group;benign breast tumors:72/266 patients with HCV infection(27%,95% CI:21.7-32.4) vs 18/95 patients(18.9%,95% CI:11-26.8) in the control group;no breast lesion 177/266(66.5%,95% CI:60.9-72.2) in patients with HCV infection vs 72/95(75.7%,95% CI:67.1-84.4) in the control group.The differences were not significant(P=NS).CONCLUSION:These results suggest that chronic HCV infection is not a strong promoter of breast carcinoma in adult females of any age.

Isolated anti-HBc is an independent risk factor for tumor recurrence in intrahepatic cholangiocarcinoma after curative resection

Background:Intrahepatic cholangiocarcinoma(ICC)is a poorly understood and aggressive malignancy with increasing incidence and mortality.Hepatitis B virus(HBV)infection is recognized as one of the important risk factors of ICC.There are few reports focusing on whether isolated antibody to hepatitis B core antigen(isolated anti-HBc,IAHBc)have prognostic role in ICC,while positive hepatitis B surface antigen(HBsAg)has been reported to be associated with the prognosis of ICC.The aim of this study was to investigate the prognostic value of IAHBc in ICC patients after curative resection,in order to identify those who have the high risk of ICC recurrence in the early stage.Methods:We divided 209 ICC patients who underwent curative resection into 4 groups:groupⅠ(n=40),HBsAg(-)/antibody to hepatitis B surface antigen(anti-HBs)(-)/anti-HBc(+);groupⅡ(n=70),HBsAg(+)/anti-HBc(-);groupⅢ(n=55),HBsAg(-)/anti-HBs(+)/anti-HBc(+);and groupⅣ(n=44),HBsAg(-)/anti-HBc(-).We compared the recurrence-free survival(RFS)and overall survival(OS)among these four groups.Results:The median follow-up time was 16.93 months(range 1-34.6 months).The 1-and 2-year RFS and OS rates were 60%and 42%,and 78%and 63%respectively in all patients.Compared to the whole non-IAHBc patients(groupⅡ+groupⅢ+groupⅣ),IAHBc patients(groupⅠ)showed significantly lower RFS at 1 year(39.8%vs.64.4%,P=0.001)and 2 years(20.7%vs.46.7%,P=0.001).When compared to other three individual groups,IAHBc patients(groupⅠ)also had the lowest RFS.We did not find significant difference in OS among the four groups.Further multivariate analysis revealed that IAHBc was an independent risk factor of RFS.Conclusions:IAHBc is an independent poor prognostic factor for tumor recurrence in ICC patients after curative resection.

Giant infected hepatic cyst causing exclusion pancreatitis:A case report

BACKGROUND An infected hepatic cyst causes clinical symptoms,such as fever and abdominal pain.A cyst with a diameter>10 cm increases the likelihood of exclusion symptoms in adjacent organs.Herein,we report a case of pancreatitis caused by an infected hepatic cyst.CASE SUMMARY The patient was an 88-year-old woman with a history of polycystic liver disease and a cyst>10 cm in diameter.She was referred to our hospital for upper abdominal pain that persisted for four days before consultation.She had a fever of 37.4℃,and a blood test showed a C-reactive protein level of 23 mg/dL.An infected hepatic cyst was diagnosed by abdominal ultrasonography,computed tomography,and magnetic resonance imaging.Antibacterial therapy and percutaneous cyst puncture did not elicit sufficient therapeutic effects.As the cyst growth continued,laparoscopic hepatic cyst fenestration was performed on hospitalization day 20.Thereafter,symptoms improved,and she was discharged on hospital day 31.CONCLUSION To our knowledge,this is the second case report of pancreatitis associated with hepatic cyst growth.Percutaneous cyst puncture and drainage or surgical therapy can be considered if a slight improvement with antibiotic therapy alone or exclusion of surrounding organs is observed.Further,attention is needed to avoid potential recurrence.

Recently acquired hepatitis C virus infection among people living with human immunodeficiency virus at a university hospital in Taiwan

BACKGROUND Little is known about the engagement in hepatitis C virus(HCV)care and completion of HCV treatment in people living with human immunodeficiency virus(HIV)(PLWH)who have HCV coinfection in the Asia-Pacific region.Examining the HCV care cascade can identify barriers to the completion of HCV treatment and facilitate achievement of HCV micro-elimination in PLWH.AIM To investigate the care cascade of incident HCV infections among PLWH in Taiwan.METHODS PLWH with incident HCV infections,defined as HCV seroconversion,were retrospectively identified by sequential anti-HCV testing of all archived blood samples at National Taiwan University Hospital between 2011 and 2018.All PLWH with incident HCV infections were followed until December 31,2019.The care cascade of HCV examined included all incident HCV-infected patients,the percentages of anti-HCV antibodies detected by HIV-treating physicians in clinical care,plasma HCV RNA load tested,HCV RNA positivity diagnosed,referral to treatment assessment made,anti-HCV treatment initiated,and sustained virologic response achieved.Those who had HCV seroconversion during the interferon(IFN)era(2011–2016)and the direct-acting antiviral(DAA)era(2017–2018)were analyzed separately.The duration of HCV viremia—from the date of seroconversion to viral clearance by treatments or until the end of observation—and the incidence of sexually transmitted infections(STIs)during the HCV viremic period were estimated.RESULTS During the study period,287 of 3495(8.2%)PLWH(92.3%being men who have sex with men)who were HCV-seronegative at baseline developed HCV seroconversion by retrospective testing of all archived blood samples.Of the 287 incident HCV infections,277(96.5%)had anti-HCV antibodies detected by HIV-treating physicians,270(94.1%)had plasma HCV RNA determined and 251(87.5%)tested positive for HCV RNA.Of those with HCV viremia,226(78.7%)were referred to treatment assessment,215(74.9%)initiated anti-HCV treatment,and 202(70.4%)achieved viral clearance.Compared with that in the IFN era,the median interval from HCV seroconversion by retrospective testing to detection of HCV seropositivity by HIV-treating physicians was significantly shorter in the DAA era{179 d[interquartile range(IQR)87-434]vs 92 d(IQR 57-173);P<0.001}.The incidence rate of STIs in the DAA vs the IFN era was 50.5 per 100 person-years of follow-up(PYFU)and 38.5 per 100 PYFU,respectively,with an incidence rate ratio of 1.31(95%confidence interval 0.96-1.77),while the duration of HCV viremia was 380 d(IQR 274-554)and 735 d(IQR 391-1447)(P<0.001),respectively.CONCLUSION While anti-HCV therapies are effective in achieving viral clearance,our study suggests more efforts are needed to expedite the linkage of PLWH diagnosed with incident HCV infections to HCV treatment.